14-(3-N-ethanolaminopropyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one | 1041860-11-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 14-(3-N-ethanolaminopropyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one
• 英文别名: 10-[3-(2-Hydroxyethylamino)propyl]-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15,17,19-nonaen-14-one
• CAS: 1041860-11-0
• 化学式: C₂₄H₂₃N₃O₂
• 分子量: 385.466
• InChiKey: DAUBQCYOPXCOBC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  65.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  14-(3-N-ethanolaminopropyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one 、 三氟乙酸 以 甲醇 为溶剂， 反应 2.0h， 以0.101 g的产率得到14-(3-N-ethanolaminopropyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trifluoroacetate
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of 14-Substituted Aromathecins as Topoisomerase I Inhibitors

  摘要：

  The aromathecin or "rosettacin", class of topoisomerase I (top1) inhibitors is effectively a "composite" of the natural products camptothecin and luotonin A and the synthetic indenoisoquinolines. The aromathecins have aroused considerable interest following the isolation and total synthesis of 22-hydroxyacuminatine, a rare cytotoxic natural product containing the 12H-5,11a-diazadibenzo[b,h]fluoren-11-one system. We have developed two novel syntheses of this system and prepared a series of 14-substituted aromathecins as novel anti proliferative topoisomerase I poisons. These inhibitors are proposed to act via an intercalation and "poisoning" mechanism identical to camptothecin and the indenoisoquinolines. Many of these compounds possess greater antiproliferative activity and anti-top1 activity than the parent unsubstituted compound (rosettacin) and previously synthesized aromathecins, as well as greater top1 inhibitory activity than 22-hydroxyacuminatine. In addition to potentially aiding solubility and localization to the DNA-enzyme complex, nitrogenous substituents located at the 14-position of the aromathecin system have been proposed to project into the major groove of the top1-DNA complex and hydrogen-bond to major-groove amino acids, thereby stabilizing the ternary complex.

  DOI：

  10.1021/jm800259e
• 作为产物：
  描述：

  14-(3-chloropropyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one 、 C.I.酸性橙108 在 sodium iodide 作用下， 以 二甲基亚砜 为溶剂， 反应 16.0h， 生成 14-(3-N-ethanolaminopropyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of 14-Substituted Aromathecins as Topoisomerase I Inhibitors

  摘要：

  The aromathecin or "rosettacin", class of topoisomerase I (top1) inhibitors is effectively a "composite" of the natural products camptothecin and luotonin A and the synthetic indenoisoquinolines. The aromathecins have aroused considerable interest following the isolation and total synthesis of 22-hydroxyacuminatine, a rare cytotoxic natural product containing the 12H-5,11a-diazadibenzo[b,h]fluoren-11-one system. We have developed two novel syntheses of this system and prepared a series of 14-substituted aromathecins as novel anti proliferative topoisomerase I poisons. These inhibitors are proposed to act via an intercalation and "poisoning" mechanism identical to camptothecin and the indenoisoquinolines. Many of these compounds possess greater antiproliferative activity and anti-top1 activity than the parent unsubstituted compound (rosettacin) and previously synthesized aromathecins, as well as greater top1 inhibitory activity than 22-hydroxyacuminatine. In addition to potentially aiding solubility and localization to the DNA-enzyme complex, nitrogenous substituents located at the 14-position of the aromathecin system have been proposed to project into the major groove of the top1-DNA complex and hydrogen-bond to major-groove amino acids, thereby stabilizing the ternary complex.

  DOI：

  10.1021/jm800259e

文献信息

• [EN] ANTI-CANCER NUCLEAR HORMONE RECEPTOR-TARGETING COMPOUNDS<br/>[FR] COMPOSÉS CIBLANT DES RÉCEPTEURS HORMONAUX NUCLÉAIRES ANTICANCÉREUX
  申请人：NUVATION BIO INC

  公开号：WO2022204184A1

  公开（公告）日：2022-09-29

  The disclosure relates to anti-cancer compounds derived from nuclear steroid receptor binders, to products containing the same, as well as to methods of their use and preparation.

  该披露涉及从核类固醇受体结合物中衍生出的抗癌化合物，包括含有相同化合物的产品，以及它们的使用和制备方法。
• Design, Synthesis, and Biological Evaluation of 14-Substituted Aromathecins as Topoisomerase I Inhibitors
  作者：Maris A. Cinelli、Andrew Morrell、Thomas S. Dexheimer、Evan S. Scher、Yves Pommier、Mark Cushman

  DOI：10.1021/jm800259e

  日期：2008.8.1

  The aromathecin or "rosettacin", class of topoisomerase I (top1) inhibitors is effectively a "composite" of the natural products camptothecin and luotonin A and the synthetic indenoisoquinolines. The aromathecins have aroused considerable interest following the isolation and total synthesis of 22-hydroxyacuminatine, a rare cytotoxic natural product containing the 12H-5,11a-diazadibenzo[b,h]fluoren-11-one system. We have developed two novel syntheses of this system and prepared a series of 14-substituted aromathecins as novel anti proliferative topoisomerase I poisons. These inhibitors are proposed to act via an intercalation and "poisoning" mechanism identical to camptothecin and the indenoisoquinolines. Many of these compounds possess greater antiproliferative activity and anti-top1 activity than the parent unsubstituted compound (rosettacin) and previously synthesized aromathecins, as well as greater top1 inhibitory activity than 22-hydroxyacuminatine. In addition to potentially aiding solubility and localization to the DNA-enzyme complex, nitrogenous substituents located at the 14-position of the aromathecin system have been proposed to project into the major groove of the top1-DNA complex and hydrogen-bond to major-groove amino acids, thereby stabilizing the ternary complex.